Experimental Allergic Encephalomyelitis (EAE) is a cell-mediated, autoimmune and demyelinating disease of the central nervous system. The disease is similar to multiple sclerosis in man. In the past, research was focused on myelin basic protein (MBP), fragments derived from it, and their respective immunological activity. An exciting development in our laboratory has been the recent demonstration in Lewis rats that the encephalitogenic sequence of synthetic peptide S49S (residues 69-84 of the MBP) houses T cell and B cell epitopes, none of which alone induces EAE. However, antibodies prepared against the C-terminal region of S49S potentiate the cell-mediated immune response to the N-terminal region of the same peptide leading to the development of EAE. The aims of the proposed research are: To prepare monoclonal antibodies against the S49S sequence using the hybridoma technology; to define the sequence boundaries and synthesize the B cell and T cell epitopes known to be present in the S49S; and to study the role of each of the anti-S49S monoclonal antibodies in the development and proliferation of specific T effector cells in autoimmune demyelination in the Lewis rat. It is anticipated that the successful completion of these studies will provide valuable information that will help elucidate the mechanism underlying EAE and clarify the role of specific antibodies in the development of disease, thus providing new insights for the control and arrest of similar demyelinating diseases in man.